p21-activated kinases (PAKs) are a family of downstream effectors of small GTPase cdc42 and rac that function as central regulators of cell motility and cytoskeletal rearrangement. Six unique PAK isoforms have been cloned that are divided into two groups, PAKs 1-3 and PAKs 4-6, based on the sequence and functional characteristics. As direct targets of Cdc42 and Rac, PAKs participate in a wide range of physiological processes beyond cell motility, including cell proliferation, apoptosis regulation, and in some systems, oncogenesis. PAK activation and overexpression has been identified in a variety of malignancies. In thyroid cancer, an increase in PAK1 expression, pPAK levels, and PAK-mediated phosphorylation of downstream effectors in the invasive fronts in aggressive papillary cancers has been reported. Thus, PAK1 represents an important therapeutic target.
P21 activated kinases (PAK) are regulators of cancer cells' structural integrity and are involved in the initiation of cell motilty and also proliferation. PAK1 is an oncogene in breast cancer and also is involved in regulating resistance of breast cancer to hormonal therapies. PAKs also are regulators of thyroid cancer invasion and progression. They have similar properties for other tumors. Thus, PAK-targeted agents may have a specific role in impairing or reversing cancer progression. To date, there are no PAK inhibitors that are FDA-approved creating an opportunity for development of new therapeutics against this key cancer target.